Rheumatoid arthritis (RA) is a complex and multifactorial autoimmune disorder with the involvement of multiple genetic and environmental factors. Genome-wide association studies (GWAS) have identified more than 50 RA genetic loci in European populations. Given the anticipated overlap of RA-relevant genes and pathways across different ethnic groups, we sought to replicate 58 GWAS-implicated SNPs reported in Europeans in Pakistani subjects. 1,959 unrelated subjects comprising 1,222 RA cases and 737 controls were collected from three rheumatology facilities in Pakistan. Genotyping was performed using iPLEX or TaqMan® methods. A total of 50 SNPs were included in the final association analysis after excluding those that failed assay design/run or postrun QC analysis. Fourteen SNPs (LINC00824/rs1516971, PADI4/rs2240336, CEP57/rs4409785, CTLA4/rs3087243, STAT4/rs13426947, HLA-B/MICA/rs2596565, C5orf30/rs26232, CCL21/rs951005, GATA3/rs2275806, VPS37C/rs595158, HLA-DRB1/rs660895, EOMES/rs3806624, SPRED2/rs934734, and RUNX1/rs9979383) were replicated in our Pakistani sample at false discovery rate (FDR) of <0.20 with nominal values ranging from 4.73E-06 to 3.48E-02. Our results indicate that several RA susceptibility loci are shared between Pakistani and European populations, supporting the role of common genes/pathways.

中文翻译：

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调查巴基斯坦人中类风湿关节炎的GWAS牵连位点。

类风湿关节炎（RA）是一种复杂的多因素自身免疫性疾病，涉及多种遗传和环境因素。全基因组关联研究（GWAS）已在欧洲人群中鉴定出50多个RA遗传基因座。考虑到RA相关基因和跨不同种族的途径的预期重叠，我们试图在巴基斯坦人中复制在欧洲人中报道的58个与GWAS相关的SNP。从巴基斯坦的三个风湿病学机构收集了1,959例无关受试者，包括1,222例RA病例和737例对照。使用iPLEX或TaqMan®方法进行基因分型。在排除未通过分析设计/运行或运行后QC分析的序列后，最终的关联分析中总共包含50个SNP。十四个SNP（LINC00824 / rs1516971，PADI4 / rs2240336，CEP57 / rs4409785，CTLA4 / rs3087243，STAT4 / rs13426947，HLA-B / MICA / rs2596565，C5orf30 / rs26232，CCL21 / rs951005，GATA3 / rs2275806，VPS37C / rs595158，HLA-DRB1 / rs660895，EOMES / rs3806624，SPRED2 / rs934734和RUNX1 / rs9979383）在我们的巴基斯坦样本中以<0.20的错误发现率（FDR）复制，标称值范围为4.73 E -06至3.48 E-02。我们的结果表明，巴基斯坦和欧洲人群之间共有多个RA易感基因座，从而支持了常见基因/途径的作用。